RGD Reference Report - The epigenetic modifier PBRM1 restricts the basal activity of the innate immune system by repressing retinoic acid-inducible gene-I-like receptor signalling and is a potential prognostic biomarker for colon cancer.

General

The epigenetic modifier PBRM1 restricts the basal activity of the innate immune system by repressing retinoic acid-inducible gene-I-like receptor signalling and is a potential prognostic biomarker for colon cancer.
Authors:	Shu, Xing-Sheng Zhao, Yingying Sun, Yanmei Zhong, Lan Cheng, Yingduan Zhang, Yixiang Ning, Kaile Tao, Qian Wang, Yejun Ying, Ying
Citation:	Shu XS, etal., J Pathol. 2018 Jan;244(1):36-48. doi: 10.1002/path.4986. Epub 2017 Nov 27.
RGD ID:	150340627
Pubmed:	PMID:28940253 (View Abstract at PubMed)
DOI:	DOI:10.1002/path.4986 (Journal Full-text)
It has long been known that patients suffering from inflammatory bowel disease (IBD) have an increased risk of developing colorectal cancer (CRC). The innate immune system of host cells provides a first-line defence against pathogenic infection, whereas an uncontrolled inflammatory response under homeostatic conditions usually leads to pathological consequences, as exemplified by the chronic inflammation of IBD. The key molecules and pathways keeping innate immunity in check are still poorly defined. Here, we report that the chromatin remodeller polybromo-1 (PBRM1) is a repressor of innate immune signalling mediated by retinoic acid-inducible gene-I (RIG-I)-like receptors (RLRs). Knockdown of PBRM1 in colon cancer cells increased the expression of two receptor genes (RIG-I and MDA5) and upregulated interferon (IFN)-related and inflammation-related gene signatures. The innate immune signal stimulated by a double-stranded RNA viral mimic was exaggerated by PBRM1 suppression. PBRM1 cooperated with polycomb protein EZH2 to directly bind the cis-regulatory elements of RIG-I and MDA5, thereby suppressing their transcription. Moreover, upregulation of RIG-I and MDA5 is required for IFN response activation induced by PBRM1 silencing. TRIM25, a protein stimulated by the RLR pathway and IFN production, physically interacted with PBRM1 and induced PBRM1 protein destabilization by promoting its ubiquitination. These findings reveal a PBRM1-RLR regulatory circuit that can keep innate immune activity at a minimal level in resting cells, and also ensure a robust inflammatory response in the case of pathogen invasion. PBRM1 was found to be downregulated in primary tissues from patients with CRC or IBD, and its expression correlated negatively with that of RLR genes and interferon-stimulated genes in CRC samples. Lower PBRM1 expression was associated with advanced pathological grade and poorer survival of CRC patients, indicating that PBRM1 could serve as a potential prognostic biomarker for CRC. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Annotation Click to see Annotation Detail View

RGD Manual Disease Annotations Click to see Annotation Detail View

Only show annotations with direct experimental evidence (0 objects hidden)

Object Symbol	Species	Term	Qualifier	Evidence	With	Notes	Source	Original Reference(s)
PBRM1	Human	colorectal cancer	severity	IEP			RGD
Pbrm1	Mouse	colorectal cancer	severity	ISO	PBRM1 (Homo sapiens)		RGD
Pbrm1	Rat	colorectal cancer	severity	ISO	PBRM1 (Homo sapiens)		RGD
PBRM1	Human	Crohn's disease		IEP		mRNA:decreased expression:colon	RGD
Pbrm1	Mouse	Crohn's disease		ISO	PBRM1 (Homo sapiens)	mRNA:decreased expression:colon	RGD
Pbrm1	Rat	Crohn's disease		ISO	PBRM1 (Homo sapiens)	mRNA:decreased expression:colon	RGD

Objects Annotated

Genes (Rattus norvegicus)

Pbrm1 (polybromo 1)

Genes (Mus musculus)

Pbrm1 (polybromo 1)

Genes (Homo sapiens)

PBRM1 (polybromo 1)

Additional Information

Gene Annotator (Functional Annotation) unavailable	Gene Annotator (Annotation Distribution) unavailable	Variant Visualizer (Genomic Variants) unavailble Variant Visualizer (Genomic Variants) unavailable
Gene Annotator (Functional Annotation)	Gene Annotator (Annotation Distribution)	Variant Visualizer (Genomic Variants)

InterViewer (Protein-Protein Interactions) unavailable	Gviewer (Genome Viewer) unavailable	Variant Visualizer (Damaging Variants) unavailble Variant Visualizer (Damaging Variants) unavailable
InterViewer (Protein-Protein Interactions)	GViewer (Genome Viewer)	Variant Visualizer (Damaging Variants)

Gene Annotator (Annotation Comparison) unavailable	OLGA (Gene List Generator) unavailable
Gene Annotator (Annotation Comparison)	OLGA (Gene List Generator)	Excel (Download)

MOET (Multi-Ontology Enrichement) unavailable	GOLF (Gene-Ortholog Location Finder) unavailable
MOET (Multi-Ontology Enrichement)	GOLF (Gene-Ortholog Location Finder)

Create Name:

Description:

Send us a Message

The epigenetic modifier PBRM1 restricts the basal activity of the innate immune system by repressing retinoic acid-inducible gene-I-like receptor signalling and is a potential prognostic biomarker for colon cancer.